Mdm10 (mitochondrial distribution and morphology 10; YAL010C) is a beta-barrel integral protein of the mitochondrial outer membrane with two distinct roles. As a subunit of the ER-mitochondria encounter structure (ERMES), it is the outer-membrane anchor on which the SMP-domain subunits Mdm34 and Mdm12 assemble with the ER-anchored Mmm1 to form bridges that tether the ER to mitochondria and transfer phospholipids between them; Mdm10 itself has no lipid-binding SMP domain. Independently, Mdm10 associates with the SAM (sorting and assembly machinery; TOB) core complex to form SAM-Mdm10, which acts in the late steps of TOM complex biogenesis: it promotes release of newly folded Tom40 from SAM, its association with Tom22 and the small Tom proteins, and membrane integration of the alpha-helical Tom22 precursor. Mdm10 is distributed throughout the outer membrane rather than being confined to ERMES foci. Loss of Mdm10 produces giant spherical mitochondria, defective mitochondrial inheritance and motility, mtDNA instability, reduced cardiolipin and increased peroxisome number, phenotypes that combine the consequences of losing ER-mitochondria tethering with defective TOM assembly. ER-mitochondria tethering by ERMES is also needed for efficient mitophagy: ERMES colocalizes with sites of mitophagosome biogenesis and contributes to formation of the isolation membrane that engulfs mitochondria.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001401 SAM complex | IBA GO_REF:0000033 | ACCEPT | Summary: SAM complex membership, phylogenetic inference within the MDM10 family. Reason: Mdm10 is a dynamic subunit of the SAM/TOB complex (SAM-Mdm10), demonstrated biochemically in yeast. Sound node placement within the fungal MDM10 family. Supporting Evidence: PMID:15239954 We have identified an unexpected subunit of the SAM complex, Mdm10, which is involved in maintenance of mitochondrial morphology. PMID:20111053 Mdm10 is distributed in the TOB complex for beta-barrel protein assembly and in the MMM1 complex for tethering of the endoplasmic reticulum and mitochondria. |
| GO:0001401 SAM complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: SAM complex membership from co-purification of Mdm10 with SAM(core) (Meisinger et al. 2007). Reason: Mdm10 associates with SAM(core) to form a distinct SAM-Mdm10 assembly complex; this is one of the two core cellular components of the protein. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0001401 SAM complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: SAM complex membership from co-purification of Mdm10 with SAM(core) (Meisinger et al. 2007). Reason: Mdm10 associates with SAM(core) to form a distinct SAM-Mdm10 assembly complex; this is one of the two core cellular components of the protein. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0001401 SAM complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: SAM complex membership from co-purification of Mdm10 with SAM(core) (Meisinger et al. 2007). Reason: Mdm10 associates with SAM(core) to form a distinct SAM-Mdm10 assembly complex; this is one of the two core cellular components of the protein. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0003674 molecular_function | ND GO_REF:0000015 | REMOVE | Summary: SGD 'no data' placeholder for molecular function. Reason: Superseded. Mdm10 now carries an experimental molecular function annotation (mitochondrion-endoplasmic reticulum membrane tether activity, IDA, Kornmann et al. 2009), so the ND statement that no molecular function information is available is no longer accurate. ND rows should not co-exist with experimental annotations in the same aspect. Supporting Evidence: PMID:19556461 Thus, one core molecular function of the Mmm1/Mdm10/Mdm12/Mdm34 complex is to connect ER and mitochondria, which can be bypassed by expressing a synthetic tether. |
| GO:0005515 protein binding | IPI PMID:15205677 Tob38, a novel essential component in the biogenesis of beta... | REMOVE | Summary: Generic protein binding from an interaction study (TOB/SAM complex study). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:15205677 Insertion of beta-barrel proteins into the outer membrane of mitochondria is mediated by the TOB complex. |
| GO:0005515 protein binding | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | REMOVE | Summary: Generic protein binding from an interaction study (SAM(core)-Mdm10 and Mdm12/Mmm1 assembly complexes). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0005515 protein binding | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | REMOVE | Summary: Generic protein binding from an interaction study (SAM(core)-Mdm10 and Mdm12/Mmm1 assembly complexes). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0005515 protein binding | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | REMOVE | Summary: Generic protein binding from an interaction study (SAM(core)-Mdm10 and Mdm12/Mmm1 assembly complexes). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0005515 protein binding | IPI PMID:20111053 Mdm10 as a dynamic constituent of the TOB/SAM complex direct... | REMOVE | Summary: Generic protein binding from an interaction study (Mdm10 in the TOB/SAM complex). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:20111053 Mdm10 is distributed in the TOB complex for beta-barrel protein assembly and in the MMM1 complex for tethering of the endoplasmic reticulum and mitochondria. |
| GO:0005515 protein binding | IPI PMID:20111053 Mdm10 as a dynamic constituent of the TOB/SAM complex direct... | REMOVE | Summary: Generic protein binding from an interaction study (Mdm10 in the TOB/SAM complex). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:20111053 Mdm10 is distributed in the TOB complex for beta-barrel protein assembly and in the MMM1 complex for tethering of the endoplasmic reticulum and mitochondria. |
| GO:0005515 protein binding | IPI PMID:20111053 Mdm10 as a dynamic constituent of the TOB/SAM complex direct... | REMOVE | Summary: Generic protein binding from an interaction study (Mdm10 in the TOB/SAM complex). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:20111053 Mdm10 is distributed in the TOB complex for beta-barrel protein assembly and in the MMM1 complex for tethering of the endoplasmic reticulum and mitochondria. |
| GO:0005515 protein binding | IPI PMID:23911324 Coupling of mitochondrial import and export translocases by ... | REMOVE | Summary: Generic protein binding from an interaction study (TOM-SAM supercomplex study). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:23911324 We show that the cytosolic domain of Tom22 links TOM and SAM into a supercomplex |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic protein binding from an interaction study (proteome-wide affinity-enrichment interactome). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MDM10's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:37968396 Affinity purification coupled to mass spectrometry is an ideal tool for such mapping |
| GO:0005741 mitochondrial outer membrane | HDA PMID:16407407 Proteomic analysis of the yeast mitochondrial outer membrane... | ACCEPT | Summary: Mitochondrial outer membrane, from outer-membrane proteomics. Reason: Mdm10 is a bona fide integral beta-barrel protein of the outer membrane; consistent with direct evidence. Supporting Evidence: PMID:16407407 the mitochondrial outer membrane not only contains resident proteins but also accumulates a conserved subclass of preproteins destined for internal mitochondrial compartments PMID:8089171 MDM10 encodes a protein of 56.2 kD located in the mitochondrial outer membrane. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:8089171 Regulation of mitochondrial morphology and inheritance by Md... | ACCEPT | Summary: Mitochondrial outer membrane (IDA), original MDM10 characterization (Sogo and Yaffe 1994). Reason: Core location: Mdm10 is an outer membrane beta-barrel protein, distributed throughout the mitochondrial network as well as in ERMES foci. Supporting Evidence: PMID:8089171 MDM10 encodes a protein of 56.2 kD located in the mitochondrial outer membrane. PMID:19556461 with the exception of Mdm10, which displayed a more widespread localization throughout the mitochondrial network |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial outer membrane, automated. Reason: Agrees with direct evidence. Supporting Evidence: PMID:8089171 MDM10 encodes a protein of 56.2 kD located in the mitochondrial outer membrane. |
| GO:0007005 mitochondrion organization | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Mitochondrion organization (IEA, InterPro) based on the classic mdm/mmm abnormal mitochondrial morphology phenotype of MDM10 mutants. Reason: Loss of any ERMES subunit converts the tubular mitochondrial network into a few giant spherical mitochondria, which is how these genes were discovered. The phenotype is real, but it is largely a downstream consequence of losing ER-mitochondria tethering and lipid supply: an artificial tether restores morphology of mdm12 and mdm34 mutants, and dominant VPS13 alleles suppress ERMES-deficiency phenotypes. The term is broad and correct at the level of necessity, but it is not the core activity, so it is kept as non-core rather than removed. Supporting Evidence: PMID:19556461 mdm12Ξ, mmm1Ξ, mdm10Ξ, and mdm34Ξ strains displayed enlarged and spherical mitochondria as compared with the tubular WT mitochondria PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function. |
| GO:0007005 mitochondrion organization | IMP PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic... | KEEP AS NON CORE | Summary: Mitochondrion organization (IMP) based on the classic mdm/mmm abnormal mitochondrial morphology phenotype of MDM10 mutants. Reason: Loss of any ERMES subunit converts the tubular mitochondrial network into a few giant spherical mitochondria, which is how these genes were discovered. The phenotype is real, but it is largely a downstream consequence of losing ER-mitochondria tethering and lipid supply: an artificial tether restores morphology of mdm12 and mdm34 mutants, and dominant VPS13 alleles suppress ERMES-deficiency phenotypes. The term is broad and correct at the level of necessity, but it is not the core activity, so it is kept as non-core rather than removed. Supporting Evidence: PMID:19556461 mdm12Ξ, mmm1Ξ, mdm10Ξ, and mdm34Ξ strains displayed enlarged and spherical mitochondria as compared with the tubular WT mitochondria PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function. |
| GO:0007005 mitochondrion organization | NAS PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch... | KEEP AS NON CORE | Summary: Mitochondrion organization (NAS) based on the classic mdm/mmm abnormal mitochondrial morphology phenotype of MDM10 mutants. Reason: Loss of any ERMES subunit converts the tubular mitochondrial network into a few giant spherical mitochondria, which is how these genes were discovered. The phenotype is real, but it is largely a downstream consequence of losing ER-mitochondria tethering and lipid supply: an artificial tether restores morphology of mdm12 and mdm34 mutants, and dominant VPS13 alleles suppress ERMES-deficiency phenotypes. The term is broad and correct at the level of necessity, but it is not the core activity, so it is kept as non-core rather than removed. Supporting Evidence: PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function. |
| GO:0007031 peroxisome organization | IMP PMID:30908556 Contribution of ERMES subunits to mature peroxisome abundanc... | KEEP AS NON CORE | Summary: Peroxisome organization (IMP): mdm10 deletion increases the number of mature peroxisomes. Reason: The phenotype is reproducible and was dissociated from respiratory defects, mtDNA loss and mitochondrial network changes, and its mechanism differs from that in mdm12 cells. No mechanism has been identified in which Mdm10 performs a step of peroxisome biogenesis or division, so this is retained as a genuine but non-core phenotype-level annotation. Supporting Evidence: PMID:30908556 First, we confirmed previous studies from other groups showing that absence of Mdm10 or Mdm12 leads to an increased number of mature peroxisomes. PMID:30908556 Finally, we present evidence that the contribution of ERMES subunits Mdm10 and Mdm12 to peroxisome number involves two different mechanisms. |
| GO:0015914 phospholipid transport | IGI PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic... | ACCEPT | Summary: Phospholipid transport (IGI) from the ERMES discovery paper. Reason: Mdm10 lacks an SMP domain and does not itself bind lipids, but it is the outer-membrane anchor of the ERMES bridge: mdm10 mutants show slowed PS-to-PC conversion, and native ER-anchored Mmm1 can serve as the sole lipid transporter (with an artificial tether) only when Mdm10 is present, i.e. Mdm10 is the mitochondrial partner the transfer machinery depends on. (Mdm10 becomes dispensable only when Mmm1 is itself artificially anchored in the outer membrane.) Mdm10 therefore contributes structure on which the transfer depends (scaffold, in the sense of the participation test), which justifies involved_in. Not used as a core molecular function for Mdm10. Supporting Evidence: PMID:19556461 Mutants of ERMES showed a two- to fivefold reduction in PS-to-PC conversion rate PMID:42095818 our results suggest that Mmm1 can act as the sole lipid transporter at the ER-mitochondrial contact sites, provided that Mdm10 is present, even in the absence of the other two subunits |
| GO:0032865 ERMES complex | IBA GO_REF:0000033 | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IBA evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IEA GO_REF:0000120 | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IEA evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:13679517 A protein complex containing Mdm10p, Mdm12p, and Mmm1p links... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:13679517 A protein complex containing Mdm10p, Mdm12p, and Mmm1p links... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0032865 ERMES complex | IPI PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch... | ACCEPT | Summary: MDM10 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MDM10 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0045040 protein insertion into mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Protein insertion into mitochondrial outer membrane, phylogenetic inference. Reason: Supported directly in yeast: SAM-Mdm10 drives the late, Tom40-specific steps of beta-barrel assembly and promotes membrane integration of the alpha-helical Tom22 precursor. Sound node placement. Supporting Evidence: PMID:15239954 Mitochondria lacking Mdm10 are selectively impaired in the final steps of the assembly pathway of Tom40, including the association of Tom40 with the receptor Tom22 and small Tom proteins, while the biogenesis of porin is not affected. PMID:20026336 The second large SAM complex, SAM-Mdm10 (mitochondrial distribution and morphology protein), binds the alpha-helical precursor of Tom22 and promotes its membrane integration. |
| GO:0045040 protein insertion into mitochondrial outer membrane | IEA GO_REF:0000104 | ACCEPT | Summary: Protein insertion into mitochondrial outer membrane, UniRule. Reason: Consistent with the experimental evidence for SAM-Mdm10. Supporting Evidence: PMID:20026336 The second large SAM complex, SAM-Mdm10 (mitochondrial distribution and morphology protein), binds the alpha-helical precursor of Tom22 and promotes its membrane integration. |
| GO:0045040 protein insertion into mitochondrial outer membrane | IMP PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet... | ACCEPT | Summary: Protein insertion into mitochondrial outer membrane (IMP), Meisinger et al. 2007. Reason: Unlike Mmm1/Mdm12, Mdm10 is a physical SAM-associated subunit acting in the Tom40-specific route, so the mutant phenotype reflects direct participation. A core process for Mdm10. Supporting Evidence: PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes |
| GO:0051654 establishment of mitochondrion localization | IMP PMID:13679517 A protein complex containing Mdm10p, Mdm12p, and Mmm1p links... | KEEP AS NON CORE | Summary: Establishment of mitochondrion localization (IMP): mitochondrial motility and inheritance defects of mdm10 cells (Boldogh et al. 2003). Reason: The motility/inheritance phenotype is real, but the 'mitochore' model that the Mmm1/Mdm10/Mdm12 complex links mitochondria and mtDNA to actin cables has been superseded by the identification of the complex as an ER-mitochondria tether. Defects in mitochondrial distribution are plausibly secondary to the collapse of the mitochondrial network into giant spheres, and ERMES-deficiency phenotypes including mtDNA loss are bypassed by VPS13 suppressor alleles. Kept as a non-core necessity annotation. Supporting Evidence: PMID:13679517 Rather, our interpretation of these observations is that Mmm1p, Mdm10p, and Mdm12p form a complex that is required to link mitochondria to actin cables, the tracks that direct mitochondrial movement from mother cells to developing daughter cells. PMID:8089171 Yeast cells with the mdm10 mutation possess giant spherical mitochondria and are defective for mitochondrial inheritance. PMID:22409400 we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against a primary role for ERMES in mitochondrial association with actin and mitochondrial movement PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function. |
| GO:0055091 phospholipid homeostasis | NAS PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch... | KEEP AS NON CORE | Summary: Phospholipid homeostasis (NAS) from the ERMES composition/topology study. Reason: ERMES mutants show reduced cardiolipin and slowed PS-to-PC conversion; these are consequences of impaired ER-to-mitochondria phospholipid transfer, which MDM10 executes as part of ERMES. The homeostasis term is a reasonable but indirect description of that role; the direct process is captured by phospholipid transport / intermembrane lipid transfer. Supporting Evidence: PMID:21945531 ERMES represents a platform that integrates components with functions in formation of ER-mitochondria junctions, maintenance of mitochondrial morphology, protein biogenesis and calcium binding PMID:19556461 A reduced rate of lipid exchange in turn slows down amino-glycerophospholipid turnover, which results in impaired CL synthesis |
| GO:0070096 mitochondrial outer membrane translocase complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial outer membrane translocase complex assembly, phylogenetic inference. Reason: Core process for Mdm10 (TOM complex assembly via SAM-Mdm10). Sound node placement. Supporting Evidence: PMID:15239954 Mitochondria lacking Mdm10 are selectively impaired in the final steps of the assembly pathway of Tom40, including the association of Tom40 with the receptor Tom22 and small Tom proteins, while the biogenesis of porin is not affected. |
| GO:0070096 mitochondrial outer membrane translocase complex assembly | IEA GO_REF:0000104 | ACCEPT | Summary: Mitochondrial outer membrane translocase complex assembly, UniRule. Reason: Consistent with experimental evidence. Supporting Evidence: PMID:15239954 Mitochondria lacking Mdm10 are selectively impaired in the final steps of the assembly pathway of Tom40, including the association of Tom40 with the receptor Tom22 and small Tom proteins, while the biogenesis of porin is not affected. |
| GO:0070096 mitochondrial outer membrane translocase complex assembly | IMP PMID:15239954 The mitochondrial morphology protein Mdm10 functions in asse... | ACCEPT | Summary: TOM complex assembly (IMP): mdm10 mitochondria are impaired in late Tom40 assembly steps. Reason: Direct evidence; Mdm10 is a SAM subunit required for association of Tom40 with Tom22 and the small Tom proteins, while porin biogenesis is unaffected. Core process. Supporting Evidence: PMID:15239954 We have identified an unexpected subunit of the SAM complex, Mdm10, which is involved in maintenance of mitochondrial morphology. PMID:15239954 Mitochondria lacking Mdm10 are selectively impaired in the final steps of the assembly pathway of Tom40, including the association of Tom40 with the receptor Tom22 and small Tom proteins, while the biogenesis of porin is not affected. |
| GO:0070096 mitochondrial outer membrane translocase complex assembly | IMP PMID:20026336 Two modular forms of the mitochondrial sorting and assembly ... | ACCEPT | Summary: TOM complex assembly (IMP): SAM-Mdm10 promotes membrane integration of Tom22. Reason: Direct evidence that SAM-Mdm10 binds the Tom22 precursor and promotes its integration, part of TOM complex assembly. Supporting Evidence: PMID:20026336 The second large SAM complex, SAM-Mdm10 (mitochondrial distribution and morphology protein), binds the alpha-helical precursor of Tom22 and promotes its membrane integration. |
| GO:0070096 mitochondrial outer membrane translocase complex assembly | IPI PMID:20026336 Two modular forms of the mitochondrial sorting and assembly ... | ACCEPT | Summary: TOM complex assembly (IPI): SAM-Mdm10 binds the Tom22 precursor. Reason: The binding of the Tom22 precursor by SAM-Mdm10 is part of the mechanism of TOM assembly. Supporting Evidence: PMID:20026336 The second large SAM complex, SAM-Mdm10 (mitochondrial distribution and morphology protein), binds the alpha-helical precursor of Tom22 and promotes its membrane integration. |
| GO:0098799 outer mitochondrial membrane protein complex | NAS PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch... | ACCEPT | Summary: Outer mitochondrial membrane protein complex (NAS), a general parent of ERMES complex. Reason: In GO, ERMES complex (GO:0032865) is a descendant of outer mitochondrial membrane protein complex (GO:0098799) (ancestor chain verified in QuickGO), so this NAS row is a correct but less specific restatement of MDM10's ERMES membership. Redundant, not wrong. Supporting Evidence: PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. |
| GO:0140474 mitochondrion-endoplasmic reticulum membrane tether activity | IDA PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic... | ACCEPT | Summary: Mitochondrion-ER membrane tether activity for MDM10, from the synthetic-tether (ChiMERA) complementation screen that defined ERMES. Reason: Kornmann et al. 2009 showed that the Mmm1/Mdm10/Mdm12/Mdm34 complex physically links the ER and the mitochondrial outer membrane and that its loss is partly bypassed by an artificial ER-mitochondria tether. Mdm10 is the beta-barrel outer membrane anchor of the bridge with which Mmm1 interacts via Mdm12 and Mdm34. The MF term describes the activity of the assembled bridge, and each subunit contributes a physically necessary part of it (ER anchor, OM anchor, or the SMP-domain bridge), so the annotation is accepted for every core subunit. GO:1990456 (the former BP for this tethering) was obsoleted in favour of this MF term (verified in QuickGO). Supporting Evidence: PMID:19556461 Thus, one core molecular function of the Mmm1/Mdm10/Mdm12/Mdm34 complex is to connect ER and mitochondria, which can be bypassed by expressing a synthetic tether. PMID:19556461 ERMES consists of the ER-resident membrane protein Mmm1 and the OMM-resident Ξ²-barrel protein Mdm10 |
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Download this section (compressed HTML)Q: What molecular activity does Mdm10 contribute to SAM-Mdm10? It regulates the timing of Tom40 release and promotes Tom22 integration, but no GO molecular function term captures this; is it best treated as a protein-folding/insertase cofactor or as a structural adaptor?
Suggested experts: Pfanner/Wiedemann lab, Endo lab
Q: How is the Mdm10 pool partitioned between ERMES and SAM, and is the partition regulated (e.g. by Tom7 or Gem1) to coordinate lipid supply with outer membrane protein biogenesis?
Suggested experts: Endo lab, Kornmann lab
Q: Should the SGD ND molecular_function row be retired now that tether activity (IDA) is annotated?
Suggested experts: SGD curators
Q: ERMES is inferred to have been present in the last opisthokont common ancestor and lost in the human lineage (Chen et al. 2026, PMID:42822426), with VPS13-family bridge proteins and other contact-site machinery likely covering ER-mitochondria lipid supply in animals. Which human proteins, if any, should receive the ERMES-equivalent function annotations, and should ERMES complex membership be explicitly excluded for human genes in phylogenetic propagation?
Suggested experts: PAINT curators, Kornmann lab
Experiment: Use separation-of-function Mdm10 mutants (guided by the in situ ERMES model and SAM-Mdm10 structures) to test whether ChiMERA rescue and Tom40 assembly can be uncoupled.
Hypothesis: Distinct Mdm10 surfaces mediate ERMES binding and SAM binding.
Type: genetic
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Download this section (compressed HTML)Moonlighting protein component of both the ERMES and SAM complex; subunit of the ERMES complex that acts as a molecular tether between the mitochondria and the ER, necessary for both efficient phospholipid exchange between organelles and for mitophagy; SAM/TOB complex subunit that functions in the assembly of outer membrane beta-barrel proteins; involved in mitochondrial inheritance and morphology; ERMES complex often co-localizes with peroxisomes adjacent to mitochondria-ER junctions
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